RAC3 down-regulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis

The nuclear receptor coactivator RAC3 plays important roles in many biological processes and tumorigenesis. We found that RAC3 is over-expressed in human chronic myeloid leukemia cells K562, which are normally resistant to TRAIL-induced apoptosis. RAC3 down-regulation by siRNA rendered these cells s...

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Veröffentlicht in:	FEBS letters 2007-10, Vol.581 (26), p.5075-5081
Hauptverfasser:	Colo, Georgina P., Rosato, Roberto R., Grant, Steven, Costas, Mónica A.
Format:	Artikel
Sprache:	eng
Schlagworte:	AIF Apoptosis Apoptosis - genetics apoptosis-inducing factor BH3 Interacting Domain Death Agonist Protein - metabolism CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism Caspases - metabolism Cell Line, Tumor Down-Regulation FLICE inhibitory protein FLIP Humans Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism Mitochondria - metabolism NF-κB Nuclear Receptor Coactivator 3 Nuclear receptors coactivator Poly(ADP-ribose) Polymerases - metabolism RAC3 receptor associated coactivator-3 Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism RNA, Small Interfering - pharmacology TNF-Related Apoptosis-Inducing Ligand - pharmacology TRAIL Transcription Factors - antagonists & inhibitors Transcription Factors - genetics Transcription Factors - metabolism tumor necrosis factor (TNF)- related apoptosis-inducing ligand Up-Regulation
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Zusammenfassung:	The nuclear receptor coactivator RAC3 plays important roles in many biological processes and tumorigenesis. We found that RAC3 is over-expressed in human chronic myeloid leukemia cells K562, which are normally resistant to TRAIL-induced apoptosis. RAC3 down-regulation by siRNA rendered these cells sensitive to TRAIL-induced cell death. In addition to the up-regulation of TRAIL receptors, the process involves Bid, caspases and PARP activation, loss of mitochondrial membrane potential, and release of AIF, cytochrome c and Smac/DIABLO to the cytoplasm. We conclude that RAC3 is required for TRAIL resistance and that this anti-apoptotic function is independent of its role in hormone receptor signaling.
ISSN:	0014-5793 1873-3468
DOI:	10.1016/j.febslet.2007.09.052